Glaucoma is an optic nerve disorder characterized by cupping of the optic nerve head and loss of peripheral vision. Occasionally there is also loss of central vision. In the majority of patients, an elevated intraocular pressure is present and is thought to contribute to the optic nerve damage. Glaucoma is the second leading cause of blindness in developed countries (Leske, M. C. (1983) Am. J. of Epidemiology 118:166-191). Its prevalence increases with age and is greater in black patients (Leske, M. C. (1983) Am. J. of Epidemiology 118:166-191). Glaucoma affects approximately 2.3 million Americans and blinds approximately 12,000 of them per year (Tielsch, J. M. (1993) Therapy for glaucoma: costs and consequences. In Transactions of the New Orleans Academy of Ophthalmologists, S. F. Ball, Franklin, R. M. (Ed.), pp 61-68. Kugler, Amsterdam).
The most prevalent form of glaucoma is primary open angle glaucoma (POAG), a progressive disease of the optic nerve characterized by degeneration and cupping of the optic nerve, loss of peripheral visual field, and increased intra-ocular pressure. Evidence indicates that POAG is genetically heterogeneous with a complex mode of inheritance. An early onset form of POAG known as juvenile open angle glaucoma (JOAG) is an autosomal dominant disorder with high penetrance.
A significant fraction of glaucoma has a genetic basis (Benedict, T. W. G. Abhaundlungen zus dem Gebiete der Augenheilkunde. Breslau: L. Freunde (1842); Stokes, (1940) W. Arch Ophthalmol 24:885-909; Kellerman, L. and A. Posner, (1955) Am. J. Ophthalmol.; 40:681-685; Becker, B., et al., (1960) Am. J. Ophthalmol. 50:557-567; Francois, J., et. al., (1966) Am. J. Ophthalmol.; 62:1067-1071; Armaly, M. F. (1967) Arch Ophthalmol; 78:35-43; Davies, T. G. (1968) Br. J Ophthalmol.:52:31-39; Jay, B., Paterson, G. (1970) Trans. Ophthalmol. Soc. U.K; 90:161-171; Paterson, G. (1970) Trans. Ophthalmol. Soc. U.K; 90:515-525; Miller, S. J. H. (1978) Trans. Ophthalmol. Soc. U.K. 98:290-292), which allows genetic methods to be used to investigate the pathophysiological mechanisms of the disease at the molecular level. The chromosomal locations of genes causing three genetically distinct types of primary open angle glaucoma have been identified (Sheffield, V., et al. (1993) Nature Genetics 4:47-50; Sunden, S. L. F., et al. (1996) 6:862-869; Richards, J. E., et al. (1994) Am. J. Hum. Genet.:54:62-70; Wiggs, J. L., et al. (1994) Genomics; 21:299-303; Stoilova, D., et al. (1996) Genomics 36:142-150; Wirtz, M. K., et al. (1997) Am. J. Hum. Genet. 60:296-304).
Therapeutics, which modulate (agonize or antagonize) genes (wild-type or mutant) involved in glaucoma, would be useful for the prevention and treatment of glaucoma. In addition, the detection of mutations in genes that correlate with the existence or a predisposition to the development of glaucoma can provide useful diagnostics.